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Sequence analysis at the level of mRNA reveals that all antibodies express the V<jats:sub>H<\/jats:sub> gene 186.2 and all but one the DF116.1 gene segment. The J segment of the heavy chain is J<jats:sub>H<\/jats:sub>2 in six cases and J<jats:sub>H<\/jats:sub>4 in two. Somatic point mutations are scarcely detectable in the antibodies, but there is extensive sequence variability at the boundaries of the D gene segment, mainly at its 5\u2032 end. However, seven of eight antibodies express tyrosine in position 99 of the heavy chain, encoded either by the 5\u2032 codon of DF116.1 or by presumed N sequences. In the former case, the tyrosine is the first of a stretch of three (positions 99\u2013101). In the latter, a similar stretch (positions 99, 101, 102) is interrupted by aspartic acid, asparagine or cysteine in position 100. These variations profoundly affect idiotypic specificity.<\/jats:p><jats:p>Six of the eight monoclonal antibodies came from mice neonatally suppressed by an anti\u2010idiotope antibody whose target idiotope is regularly expressed in primary anti\u2010NP responses and depends upon a non\u2010germ\u2010line\u2010encoded aspartic acid in position 100 of the heavy chain. The sequence data show that the mice circumvent suppression by expressing antibodies which lack this aspartic acid but are otherwise structurally very similar to anti\u2010NP antibodies from normal animals. Since suppression in the animals is partly controlled by regulatory T cells, we conclude that these T cells are highly restricted in their specificity in that they preferentially see a determinant which also depends upon the aspartic acid in position 100. The data suggest that the V<jats:sub>H<\/jats:sub> to D boundary serves as a target of idiotypic selection.<\/jats:p>","DOI":"10.1002\/eji.1830150517","type":"journal-article","created":{"date-parts":[[2007,2,28]],"date-time":"2007-02-28T21:52:46Z","timestamp":1172699566000},"page":"512-520","source":"Crossref","is-referenced-by-count":151,"title":["Structure of primary anti\u2010(4\u2010hydroxy\u20103\u2010nitro\u2010phenyl)acetyl (NP) antibodies in normal and idiotypically suppressed C57BL\/6 mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Ana","family":"Cumano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.145.6.1559"},{"key":"e_1_2_1_3_2","first-page":"511","volume":"5","author":"Eichmann K.","year":"1975","journal-title":"J. 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